Lung cancer is the leading cause of cancer deaths in the United States and worldwide. The tumor suppressor gene Liver Kinase B1 (LKB1), also known as Serine/Threonine Kinase 11 (STK11), encodes a serine/threonine kinase that is critical for cellular metabolism, polarity and growth control. LKB1 gene is somatically inactivated in approximately 30% of non-small cell lung cancer (NSCLC) cases and third most frequently mutated gene in NSCLC. The loss of LKB1 in the context of Kirsten rat sarcoma viral oncogene (KRAS) mutations promotes lung cancer metastasis in mouse models and is associated with poor prognosis. The LKB1 status is linked with cancer responsiveness to several targeted agents and chemotherapy in mouse tumor models. LKB1 is thus implicated as diagnostic, prognostic and predictive biomarkers in human lung cancer. Moreover, LKB1 mutations have been observed in other tumor types such as ovarian cancers and cervical cancers, and are important for tumor progression. However, clinical benefits that exploit LKB1 deficiency cannot be achieved without studying the tumors produced by LKB1 loss of function.